Increased Neutrophil Migration Research Articles

Evaluation of the effect of azapropazone on neutrophil migration in anaesthetized swine using a multichamber blister suction technique

1. The purpose of this study was to determine the in vivo inhibitory efficacy of azapropazone on neutrophil migration. The effects of azapropazone given at a dose of 100 mg kg-1 i.v. every 2 h on the neutrophil migration into skin inflammation sites (blister fluid) as well as into an autologous serum (+/- chemoattractant) placed above the blister surface (2nd chamber) were determined. 2. Azapropazone treatment schedule maintained blood levels at 70-100 micrograms ml-1 throughout the time course (360 min) of the experiment. 3. Azapropazone significantly inhibited (48 +/- 6%) neutrophil migration into the blister fluid (as evident from the decrease in myeloperoxidase activity). 4. Azapropazone significantly inhibited the neutrophil migration into the autologous serum either with (65 +/- 5%) or (35 +/- 6%) without the chemoattractant, formyl-methionyl-leucyl-phenylalanine (FMLP). The chemoattractant, FMLP, markedly increased neutrophil migration into the autologous serum by approximately 1.5 to 2 times the non-FMLP treated group. Azapropazone was more efficacious in inhibiting the neutrophil migration in the presence of FMLP than in its absence. 5. We conclude that azapropazone is an effective inhibitor of neutrophil migration into topically inflamed sites in anaesthetized swine.

Effect of human serum and some of its components on neutrophil adherence and migration across an epithelium.

The effect of human serum and some of its components on the process of transepithelial migration of human neutrophils was investigated in an in vitro system. 10% autologous serum caused an increase in neutrophil adherence to and migration across canine kidney epithelial cells. This increase in neutrophil binding also occurred if the epithelium but not the neutrophils had been preincubated with serum. The binding was lost if the serum was either preabsorbed over the kidney epithelium before use or heat inactivated. Indirect immunofluorescence studies indicated that IgG, IgM, and a component of C3 bound to the epithelial surface, whereas IgA, IgE, or C5a were not detectable. The majority of epithelial cells were immunofluorescent, however epithelial cells with varying degrees of reactivity were also apparent and approximately 5% of the epithelial cells did not bind IgG, IgM, and C3. When epithelia were simultaneously tested for the presence of either IgG, IgM, or C3, and bound neutrophils the few epithelial cells which did not bind IgG or IgM also did not bind C3 or neutrophils. Studies with monoclonal antibodies against Fc and C3 receptors indicate that neutrophil adherence to the epithelial surface was mediated predominately by the receptors for C3b and C3bi. In response to a chemotactic gradient, bound neutrophils were able to detach and migrate across the epithelium. A separate heat-stable factor(s) in serum was able to increase neutrophil migration across the epithelial monolayer. This factor acted independently of the factors which caused the increase in neutrophil binding as the increase in neutrophil migration also occurred under conditions (preabsorption over the kidney epithelium or heat inactivation) that prevented the increase in neutrophil binding. The increase in neutrophil migration may be caused by the permeability-increasing properties of this factor as both serum and heat-inactivated serum lowered the transepithelial electrical resistance an average of 38 and 35%, respectively, in 40 min. Upon removal of serum or heat-inactivated serum, the resistance returned 100 and 81%, respectively, in 5 h.

Bowel-associated dermatosis-arthritis syndrome. Immune complex-mediated vessel damage and increased neutrophil migration.

In a recent report we described a syndrome, identical to bowel-bypass syndrome, that occurred in four patients who had not had bypass surgery. Herein, circulating immune complexes (CICs) and neutrophil migration are evaluated in three of those four patients to test the hypothesis that the cutaneous lesions might have resulted from interaction between immune complex-mediated vessel damage and increased neutrophil migration. In vitro assays indicated that CICs were present in one of two patients and "histamine trap" test evidence for CICs was present in both patients tested. Although serum from the three patients appeared to increase neutrophil movement, statistically significant increases were not observed when data were pooled in this small study group. Preliminary results suggest that immune complex-mediated vessel damage, followed by extensive accumulation of neutrophils, may cause the pustular vasculitis in the bowel-associated dermatosis-arthritis syndrome.

Hereditary cataplexy.

<h3>ABSTRACT</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Neutrophils are believed to play an important role in both the initiation and progression of RA, and large numbers of activated neutrophils are found within both synovial fluid (SF) and synovial tissue from RA joints. In this study we analysed paired blood and SF neutrophils from patients with severe, active RA (DAS28&gt; 5.1, n=3) using RNA-seq. 772 genes were significantly different between blood and SF neutrophils. IPA analysis predicted that SF neutrophils had increased expression of chemokines and ROS production, delayed apoptosis, and activation of signalling cascades regulating the production of NETs. This activated phenotype was confirmed experimentally by incubating healthy control neutrophils in cell-free RA SF, which was able to delay apoptosis and induce ROS production in both unprimed and TNF<i>α</i> primed neutrophils (p&lt; 0.05). RA SF significantly increased neutrophil migration through 3mM transwell chambers (p&lt; 0.05) and also increased production of NETs by healthy control neutrophils, including exposure of myeloperoxidase (MPO) and citrullinated histone-H3-positive DNA NETs. IPA analysis predicted NET production was mediated by signalling networks including AKT, RAF1, SRC and NF-<i>κ</i>B. Our results expand the understanding of the molecular changes that take place in the neutrophil transcriptome during migration into inflamed joints in RA, and the altered phenotype in RA SF neutrophils. Specifically, RA SF neutrophils lose their migratory properties, residing within the joint to generate signals that promote joint damage, as well as inflammation via recruitment and activation of both innate and adaptive immune cells. We propose that this activated SF neutrophil phenotype contributes to the chronic inflammation and progressive damage to cartilage and bone observed in patients with RA.