Pigeon Serum Research Articles

Experimental granulomatous lung disease in guinea pigs. Morphology and collagen analysis.

Chronic granulomatous lung disease was produced in immunized guinea pigs using aerosol exposure to pigeon serum at intervals of four weeks. Initially, animals developed a hemorrhagic alveolitis with polymorphonuclear leukocytes. After the second exposure, animals had a mononuclear alveolitis with ill-defined granulomata. Animals sacrificed after the third or fourth aerosol exposure had well-defined granulomata with varying degrees of interstitial fibrosis. Chemical estimates of total lung collagen showed increased lung collagen after the third and fourth exposure. Whereas animals sacrificed within one week after the second or third exposure had no increase in collagen concentration, animals sacrified 4 weeks after these exposures did. There was also a correlation between the morphologic and chemical estimates of lung collagen. These data suggest that repeated aerosol exposure of guinea pigs to a soluble antigen at intervals can result in chronic granulomatous lung disease that is characterized by morphologic and chemical increases in lung collagen. This model may be of value in defining immune and connective tissue alterations in granulomatous lung disease.

A new disease: a nasal form of pigeon breeder's disease.

In 47 allergic rhinitis patients regularly exposed to pigeons, nasal provocation tests with pigeon dropping extracts, in combination with other parameters, were performed. Twenty-five of the 47 patients developed a late nasal response (LNR) to pigeon droppings (53%), six of them an isolated response and 19 a dual response (immediate + late). The precipitating antibodies to pigeon droppings were positive in 20 (80%) and to pigeon serum in nine LNR patients (36%). Late skin responses to pigeon droppings occurred in 15 (60%) and to pigeon serum in seven LNR patients (28%). In 13 patients (52%) general malaise, in seven (28%) increased blood eosinophilia, in nine (36%) increased body temperature and in 11 (44%) haemorrhages in the nasal mucosa were observed during the LNR. The results of this study provide evidence for the existence of a new disease, a nasal form of pigeon breeder's disease.

The late bronchus-obstructive response to bronchial challenge with pigeon faeces and its correlation with precipitating antibodies (IgG) in the serum of patients having long-term contact with pigeons.

From a total of 160 patients with allergic bronchial asthma or chronic asthmatic bronchitis, eighteen (11.3%) patients reported being regularly exposed to pigeons. In these eighteen patients, bronchial provocation tests with pigeon faeces were performed and the precipitating antibodies (IgG) in their serum against pigeon faeces and serum were estimated. Of the eighteen patients, seven (39%) demonstrated a 'late bronchus-obstructive response' to pigeon faeces. Three patients developed only an 'isolated late response' and in the other four patients the late response occurred as a part of the 'dual response'. In the seven patients with the positive late bronchial response, the precipitating antibodies in their serum to pigeon faeces were positive in five (71%) and to pigeon serum in two (28%) of them. The late skin responses to pigeon faeces were positive in five (71%) patients, the blood eosinophilia increased in six (86%) of them, a slight pyrexia occurred in two (28%) and general malaise symptoms appeared in six (86%) of them. None of these patients developed changes on the chest X-ray during the late response. The remaining eleven patients did not develop any bronchial response to pigeon faeces challenge, although in six (55%) of them the late skin responses were positive, and two (18%) had precipitating antibodies in the serum to pigeon faeces and one (9%) to pigeon serum. It is concluded that positive precipitating antibodies in the serum to pigeon faeces and serum are important parameters for detection of pigeon breeder's disease in exposed individuals, however confirmation of this diagnosis should be provided by the bronchial provocation tests.

Serum antibodies to pigeon antigens in smokers and nonsmokers.

Antibodies to pigeon antigens were determined by double immunodiffusion and ELISA in 80 pigeon breeders without pigeon breeder's disease. Precipitating antibodies to pigeon serum and droppings were found in 5 and 8%, respectively, of 39 breeders who were smokers and in 46 and 51%, respectively, of 41 breeders who were nonsmokers (p less than 0.001). By ELISA, IgG antibodies to pigeon serum and droppings were detected in 44 and 54%, respectively, of smokers and in 81 and 85%, respectively, of nonsmokers (p less than 0.01). The antibody titres were generally higher in nonsmokers than in smokers. These findings may partly explain why allergic alveolitis occurs most often in nonsmokers.

Elevation of serum chemotactic factor inactivator activity during acute inflammatory reactions in patients with hypersensitivity pneumonitis.

Inflammatory mediators such as the vasoactive and chemotactic factors derived from the activation of the complement system are extremely potent biological peptides that are under rigid control of specific serum-derived regulators, e.g., the anaphylatoxin inactivator (AI) and the chemotactic factor inactivator (CFI). We have previously demonstrated that serum chemotactic factor inactivator concentrations are altered during chronic inflammatory states; here we demonstrate that a rapid elevation of serum CFI activity occurs during acute inflammatory reactions in patients suffering from hypersensitivity pneumonitis. Specifically, serum CFI concentrations were evaluated in patients with hypersensitivity pneumonitis (pigeon breeder's disease) and control subjects (asymptomatic) after aerosol challenge with 2 ml of sterile pigeon serum. At 4 h postchallenge, serum CFI concentrations in the patients with hypersensitivity pneumonitis increased rapidly to 3 times the prechallenge serum concentrations. Asymptomatic (control) subjects showed no increase in serum CFI concentrations after exposure to pigeon serum. In independent studies, we have also demonstrated that serum CFI concentrations are elevated in (1) rabbits with glycogen-induced peritonitis, (2) rabbits after intravenous infusion of C5-derived chemotactic factors, and (3) patients undergoing hemodialysis. These combined data clearly demonstrate that serum CFI activity is rapidly elevated during acute inflammatory reactions within both patient and animal populations, and suggest that serum CFI may represent a "hyperacute" phase reactant that is elevated during inflammation. Possibly, this elevation of CFI may be induced in response to inflammatory mediators produced during inflammation. Thus, the acute elevation of serum CFI concentrations that occurs during acute inflammation may represent the control system that would be responsive to the regulatory needs of the body during inflammatory reactions.

Antibody against a pigeon bloom-extract: a further antigen in pigeon fanciers' lung.

Pigeon bloom, a waxy powder which coats the feathers of racing pigeons, has been investigated as a potential antigen in pigeon fanciers' lung. Precipitins to a soluble bloom-extract were demonstrated in fifty-nine of ninety-seven people studied at two Scottish-pigeon shows, whilst precipitins to pigeon serum were found in thirty-seven. A radioimmunoassay was developed to allow an estimation of the intensity of antibody response to this antigen in nineteen pigeon fanciers being investigated for pigeon fanciers' lung. The mean antibody level to bloom extract was significantly higher (P less than 0.05) in those with acute symptoms compared to those with less severe symptoms. Pigeon bloom is a highly antigenic material and provides an alternative to pigeon droppings as a source for the inhalant antigens regularly encountered by those keeping pigeons.

Hypersensitivity pneumonitis in nonhuman primates. I. Studies on the relationship of immunoregulation and disease activity.

We investigated the relationship of immunoregulation to disease activity in a nonhuman primate model of pigeon breeder's disease. Two Macaca arctoides monkeys developed classical symptoms of hypersensitivity pneumonitis after sensitization and prolonged bronchial challenge, whereas 2 other monkeys remained asymptomatic after in vivo challenge. There were no differences in the percentages of T cells, B cells, monocytes, or FC gamma-bearing T cells between symptomatic and asymptomatic animals. Nonetheless, we found a population of concanavalin A-induced, pigeon serum- (PS) induced, and spontaneous T cells that functioned as suppressor cells in autologous in vitro co-cultures in asymptomatic animals that were missing or nonfunctional in symptomatic animals. Monocyte suppressors functioned in both groups. We used low-dose total body irradiation (TBI) to inactivate T suppressor cells. Fifteen radiation units of TBI caused no change in the physical activity, routine chemistries, or blood counts of the 4 animals. After TBI, however, the previously asymptomatic animals developed fever, tachypnea, and signs of pulmonary congestion after in vivo challenge with PS. There was no change in the response to challenge in the symptomatic group. This altered response to in vivo challenge in the previously asymptomatic group persisted for 2 wk after TBI. During this period the difference in vitro immunoregulatory activity between Con A-induced, PS-induced, and spontaneous T cells in symptomatic and asymptomatic animals disappeared. Monocyte suppressors, however, continued to function in both groups after TBI. These data suggest that the monkey is an appropriate model for studies of human HP and that T cell immunoregulation may be an important element in the pathogenesis and disease activity of HP.

Immunoregulation in hypersensitivity pneumonitis. I. Differences in T-cell and macrophage suppressor activity in symptomatic and asymptomatic pigeon breeders.

Cell-mediated immunity delineates symptomatic from asymptomatic pigeon breeders better than the presence of precipitating antibodies or HLA haptotypes. We therefore investigatedin vitro lymphocyte function in asymptomatic and symptomatic pigeon breeders. Peripheral blood, T, B, and adherent numbers were equal in both groups. Although the response to an optimum dose of concanavalin A was similar in both groups, the asymptomatic group revealed a reduced response to an optimum concentration of phytohemagglutinin and pokeweed mitogen. This decreased mitogen-induced proliferation was abrogated if cells from asymptomatic patients were precultured in medium alone for 48 hr before stimulation. A similar preincubation procedure, however, decreased the response to subsequent mitogenic stimulation in the symptomatic patients. As this suggested the possibility of heightened immunosuppression in the asymptomatic group, suppressor cells were studied. The numbers of FCγ-bearing T cells were similar in both groups and did not differ from control values. In addition, concanavalin A-induced suppressor-cell activity did not differ in either group. Nonetheless, fresh T cells, adherent cells, and peripheral blood mononuclear cells (PBMC) preincubated with pigeon serum decreased the response of preincubated autologous PBMC to mitogens and antigens in asymptomatics. A similar suppression did not occur in autoch-thonous cocultures of PBMC from symptomatic patients. These data suggest that there may be cellular suppressor influences in the asymptomatic group which are absent or nonfunctional in the symptomatic patients. Although this may be useful in distinguishing between the groups, the relationship of these suppressor cells, if any, to the pathogenesis of hypersensitivity pneumonitis awaits further study.

Prevalence of precipitins in groups at risk of developing hypersensitivity pneumonitis.

A study was made of the prevalence of serum precipitins to Micropolyspora faeni, Thermoactinomyces vulgaris, Aspergillus fumigatus, and pigeon serum in population groups suspected to be at high risk for the development of hypersensitivity pneumonitis. Pigeon breeders' sera contained precipitins mainly to pigeon serum (38%) and A. fumigatus (18%). Occupants of homes in which forced air heating systems were investigated for the presence of microorganisms reacted mostly with M. faeni (13%) and A. fumigatus (8%). Individuals from environments where several cases of hypersensitivity pneumonitis were discovered reacted largely with M. faeni (28%) and T. vulgaris (21%). Sera supplied by physicians from patients with respiratory symptoms reacted primarily to A. fumigatus (24%) and to a lesser extent to M. faeni (16%) and T. vulgaris (9%). The results indicate that the prevalence of precipitins to the tested antigens is not uniform and may be influenced by the environment. Furthermore, the prevalence of precipitins in groups at risk is greater than previously reported for the normal population.

IgA and IgG antibody activities of serum and bronchoalveolar fluid from symptomatic and asymptomatic pigeon breeders.

Serum IgA and IgG antibody activities against pigeon serum were measured in 16 symptomatic pigeon breeders, 20 asymptomatic pigeon breeders, and 3 normal subjects by radioimmunoassay. The IgA and IgG antibody activities against pigeon antigen of the group of patients with disease was significantly greater than those of patients in the asymptomatic and the control group. The overlap of results for the symptomatic and asymptomatic breeders limits the diagnostic value of these individual IgA or IgG antibody determinations. Bronchoalveolar fluid and serum samples from a smaller group of pigeon breeders who underwent lung lavage were available for studies of antibody activity against pigeon serum. Ten asymptomatic and 6 symptomatic breeders were available for study. Both IgG and IgA antibody activities were detected by radioimmunoassay in serum samples and bronchoalveolar fluid. The IgA antibody activity determined by the radioimmunoassay was higher in the respiratory secretions.

Cholesterol esterification and cholesteryl ester accumulation in cultured pigeon and monkey arterial smooth muscle cells

Aortic smooth muscle cells from atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons were grown in culture utilizing conditions identical to those developed for the culture of rhesus monkey arterial smooth muscle cells and skin fibroblasts. Pigeon smooth muscle cells had ultrastructural and growth characteriscis similar to mammalian smooth muscle cells in culture including growth in multiple overlapping layers, numerous pinocytic vesicles, and abundant myofilaments. Cells were incubated for 24 to 72 hr with culture medium containing either lipoprotein deficient serum, fetal calf serum, normocholesterolemic pigeon serum or hypercholesterolemic pigeon serum, and differences in cholesterol content and in the rate of cholesterol esterification were studied. Although there was substantial variability in the absolute cholesterol content among different cell lines, cells of the same type behaved similarly in their response to the various test sera. Generally, the higher the cholesterol content of the culture medium the greater the cholesterol content of the cells. There were, however, considerable differences in the magnitude and pattern of response among the different cell types. Incubation with 10% hypercholesterolemic serum resulted in an increase of similar magnitude in the free cholesterol content of all cell lines. This was not true, however, for the accumulation of cholesteryl esters. Incubation with 10% hypercholesterolemic serum produced a marked increase in the cholesteryl ester content of monkey skin fibroblasts and smooth muscle cells while producing only a slight increase in the cholesteryl ester content of pigeon smooth muscle cells unless very high concentrations of hypercholesterolemic serum were used. Monkey skin fibroblasts were the most responsive to cholesteryl ester accumulation with a greater than 28-fold increase in cholesteryl ester content occurring when incubated with hypercholesterolemic serum. Incubation for 24 hr with hypercholesterolemic serum stimulated cholesterol esterification 4 to 8-fold in monkey cells in a manner that paralleled the time course of accumulation of cholesteryl esters, while no stimulation in cholesterol esterification occurred in pigeon cells, consistent with their lack of ability to accumulate large amounts of cholesteryl esters. No differences in the response to either normal or hypercholesterolemic serum were seen between smooth muscle cells from atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons. There were, however, major differences between pigeon and monkey cells. Although results indicate that the mechanism of accumulation of cholesteryl esters by pigeon smooth muscle cells may be different than for mammalian cells, no differences were seen in any of the parameters measured that might help to explain the difference in susceptibility to atherosclerosis of the two breeds of pigeons.

Antibodies against Purified Pigeon IgA in Pigeon Breeders' Disease

It is demonstrated that previously described PDF1-A antigens from pigeon dropping extract contain pigeon IgA. The sera of patients with pigeon breeders' disease contain precipitating antibodies against pigeon IgA, in contrast to the sera of pigeon breeders suffering from unrelated forms of pulmonary dysfunction. The degree of complement consumption by PDF1A antigens, pigeon serum, and pigeon IgA turned out to be correlated. No correlation was found between precipitating anti-pigeon IgA antibodies and complement consumption by pigeon IgA in patients' sera.

Precipitation of animal plasma proteins by puff-adder venom

1. 1. Plasma and serum samples obtained from various animals never previously exposed to snakes or snake venom were diffused against different concentrations of puff-adder, Bitis arietans, venom using the double immunodiffusion technique. 2. 2. Depending upon venom concentration, two precipitin arcs could be produced in the case of all plasma samples used. No serum samples showed any arcs except pigeon serum, where one precipitin line was observed. 3. 3. By altering the concentration of snake venom between 1% and 10% when immunodiffusing against plasma a change in position of the precipitin lines was observed and also the disappearance of one or both of the two bands at higher concentrations. This indicates that the arcs observed are in all probability due to precipitation of plasma protein fractions. 4. 4. Previous results indicated that one of the two bands observed when diffusing venom against plasma was due to the precipitation of fibrinogen. By diffusing snake venom against heparin we have now shown that the second band involves this molecule and is not due to another coagulation factor as was suggested previously.

Local Pulmonary Immunity in Pigeon Breeder's Disease

We studied pulmonary and systemic aspects of the immune response in a patient with pigeon breeder's disease before and after an inhalation challenge with pigeon serum. Macrophage migration inhibition was induced with bronchoalveolar wash cells exposed to both pigeon serum and pigeon dropping extract before but not after challenge. Peripheral blood lymphocytes exposed to these antigens did not induce inhibition of guinea pig peritoneal macrophage migration before challenge. However, after challenge peripheral blood lymphocytes did cause macrophage migration inhibition when exposed to pigeon serum. Both systemic and bronchoalveolar lymphocytes proliferated when exposed to these pigeon antigens in vitro. Our patient represents the first reported case of lymphokine production by pulmonary as well as systemic lymphocytes in hypersensitivity pneumonitis.

Hypersensitivity lung disease: Early diagnosis

The early diagnosis of hypersensitivity lung disease (HLD) is important because of its progressive morbidity. It is often difficult to establish the diagnosis in the early stages because of the absence of defined symptoms. Case histories of 2 patients with pigeon breeder's HLD are reported. Both patients presented with unusual manifestations of the disease: one patient was asymptomatic but had an abnormal chest radiograph; the other patient had a normal chest radiograph but experienced occasional symptoms of exertional dyspnea. Both patients had abnormal pulmonary function and precipitin bands against pigeon serum. Following inhalation challenge with pigeon serum both patients developed fever and leukocytosis, but no significant pulmonary function response was observed. In both patients pulmonary function tests returned to near normal levels after corticosteroid therapy. Early detection of HLD may prevent progressive irreversible pulmonary damage. This requires a high index of clinical suspicion and appropriate screening tests. Inhalation challenge procedures are useful in establishing the diagnosis.

PRECIPITIN TEST IN FARMERS IN MOUNTAIN DISTRICT OF WEST JAPAN WITH 14 FUNGUS AND OTHER ORGANIC ANTIGENS

Two hundreds and seventy one cases of sera of farmers (48.8±10.8 yr.) in mountain district of Kumamoto prefecture were examined by gel diffusion test for precipitins to M. faeni, T. vulgaris and other 12 antigens of fungus and pigeon proteins.Ten positive sera (3.7%) from 271 sera tested were detected to M. faeni and 13 were to T. vulgaris. The confidence intervals (95%) of the positive ratiowas calculated 1.8%-6.6%and 2.3%-7.4%, respectively. To other 10 antigens 1-22 sera were positive, such as C. corticale (0.1%-2.7%, as confidence intervals), S.granarius (4.9%-11.4%), P. pullulans (0.4%-3.7%), Aspergillus mix (0.6%-4.2%), Pigeon serum & droppings (0.2%-3.1%), C. acremonium (0.8%-4.7%), T. viride (0.0%-2.0%), Candida (1.6%-6.2%) and P.casei (0.2%-3.1%). NO cases were positive toCladsporium and Alternaria. And 61 cases (17.5%-27.5%) were positive to at least one antigen of all 14 tested.There was no significance of the proportions of positive reactions between male and female, or age groups. But higher percentagewas found in farmers longer experience of works with hay, straw and compost. Thepresence of a positive precipitin test has been considered as unsatisfactory criterion for the diagnosis of the farmer's lung. However, the findings of our survey suggest that farmers in West Japan has been exposed relatively high amount and/or various kinds of fungus antigens throughout the farm works with hay, straw and compost.

Pigeon breeder's disease. Antibody response of man against a purified component of pigeon dropping extract

A homogeneous component of pigeon dropping extract, one of the etiologic agents of pigeon breeder's disease (PBD), was used to evaluate some of the antibody responses using serum from patients with PBD. Their responses were compared with those of similarly exposed, but asymptomatic, pigeon breeders. As assessed by antigen-binding capacity, quantitative precipitation, and complement fixation, the responses from these two groups were qualitatively similar. In general, these results are in agreement with other studies using pigeon serum components. Since symptomatic and asymptomatic pigeon breeders are not readily discriminated by results of tests for humoral immunity, we suggest that other factors are important in the pathogenesis of PBD.

Three Immunoglobulin Classes in the Pigeon <i>(Columbia livia)</i>

Three classes of immunoglobulins have been identified in the pigeon. IgG and IgM were purified from pigeon serum whereas IgA was isolated from pigeon hepatic bile. Pigeon IgG and IgM had the same properties and immunohistological distribution as their chicken homologues. Pigeon IgA was identified on the following grounds: (1) it contains the same light chains as pigeon IgM and IgG; (2) it is relatively abundant in exocrine secretions such as bile, egg white, cropmilk and intestinal fluid, whereas it is present only in small amounts in serum; (3) it occurs in the cytoplasm of the majority of the immunocytes from the intestinal mucosa; (4) its electrophoretic mobility and molecular size are similar to those of chicken IgA. Surprisingly, no immunoglobulin-containing cells could be detected in sections of the wall of the cropmilk gland, despite the high IgA content of the cropmilk.

The P Blood Group System in Pigeon Breeders and Pigeon Breeder's Disease

A blood group P1-like antigen has been found in gram-negative bacilli isolated from pigeon droppings, in pigeon serum, and on pigeon red blood cells. As a probable resident of the environment of the pigeon loft, the antigen stimulated formation of anti-P1 antibody in eight of 11 pigeon breeders who belonged to the P2 blood group. Only one of 11 random hospitalized patients with the P2 blood phenotype had a detectable titer of anti-P1 antibody (P less than 0.01). The titer of anti-P1 antibody was not significantly different in symptomatic vs asymptomatic breeders. The presence or absence of anti-P1 antibody could not be correlated with any band of immunoprecipitates formed between pigeon breeder's serum and crude extract of pigeon droppings. The P antigen was identified in pigeon-dropping extracts of breeders with the P2 blood phenotype by inhibition of hemagglutination. We conclude that anti-P1 antibodies appear to be a component of the immunologic response to avian antigens of pigeon breeders but are probably unrelated to the pathogenesis of pigeon breeder's disease.

Childhood Hypersensitivity Pneumonitis Due to Dove Antigens

A case of hypersensitivity pneumonitis due to doves is reported and compared with other cases due to dove or pigeon antigens reported in children. The diagnosis is substantiated by the presence of precipitating antibody to dove and pigeon serum, clinical improvement after contact with the doves was broken, and a positive response to inhalation challenge with pigeon serum. The insidious nature of this disease is emphasized as well as the importance of having detailed environmental information in children with unexplained respiratory disease.