SP-A-like molecule may be a marker of the lung-colon connection in IBD

Abstract

According to Chinese Medicine, lung and colon is a pair of external-internally related organ systems. It means that a lung disease often have colon syndromes whereas a colon disease may have lung syndromes. In clinic, epidemiological and clinical investigation showed that many colon diseases were often accompanied by the pulmonary involvement, and many lung sources of non-specific environmental exposure, smoking stimulation or disorders were also had the colon involvement and vice versa. To date, it remains neither lung nor colon is the primary or secondary injury site. Although there is lots of clinic evidence of lung-colon connection, the laboratory evidence still remains to investigation. Inflammatory bowel disease (IBD), a term that describes two diseases characterized by aberrant immune response of the intestinal mucosa: Crohn's disease (CD) and ulcerative colitis (UC) may be a good example to study lung-colon connection. The reason is that both CD and UC often have pulmonary involvement, and non-specific environmental exposure and smoking contribute the pathogenesis of IBD. The understanding mechanism is that the complicated immunological, environmental and genetic factors should trigger lots of molecular events. Because both lung and colon has a huge vulnerable biological surface and which is continuously exposed to the external environment, frontier host defense molecules play dominant role to balance the open body systemic response. In this study, we investigated one of frontier host defense molecules, surfactant protein A (SP-A) expression in normal, inflammatory and IBD area, In the distal terminal (normal), the SP-A like immunoreactivity was only found at the apical part of epithelia, connective tissue of mucosa and submusoca. In the inflammatory (surround of IBD) area, strong staining was found not only at the apical part of epithelia, connective tissue of mucosa and submusoca, but also in chronic inflammatory cell of lamina propria and submucosa. In CD and UC area, even some epithelia of crypt of Lieberkühn are positive. The staining in IBD area is much stronger than inflammatory area, and the staining in inflammatory area is much stronger than normal area. Physicians believe the body (internal environment) is a society, the Traditional Chinese Medical Scholars even believe the body and external environment is a society. Drs. Whittaker and Hynes analyzed 948 proteins containing 1196 von Willebrand Factor A (vWFA) domain members, they found the majority of members in the family are located in the extracellular matrix with restricted expression in a special kind of tissue in an organ, or a special kind of tissue in many organs, or in circulated blood. The members in the cell membrane or cytoplasm or nucleus are involved in cellular functions such as gene transcription, DNA repair, ribosomal and membrane transport, and proteasome activity. The family members may form a multiprotein complex. We also found IR-SP-A was compatible with the sites, theoretically containing collagenous and lectin domain molecules, also compatible with the primary injury sites of some autoimmune diseases. In this study, we are note the staining signal is SP-A or SP-A like molecules, we do know the positive signal can be blocked by SP-A antigen from recombinant or bronchoalveolar lavage (BAL), it should be containing collagen or lectin domain proteins. Tightly regulated distribution of family members of proteins is related to social property in the open body system. In this opinion, the mechanism of complicated communication of lung-colon may associate with the social property of cell and molecule. Research scientists need to pay more attention on social property of cells and proteins. Our previous study found the distribution of IR-SP-A in colon was compatible with the primary injury sites of some autoimmune diseases including IBD. Clinical observable lung-colon connection as a complex cellular and molecular event remains a long way to establish. It should be a complicated communication. It is most likely to activation the communication between local and system. To our knowledge, however, thus far it remains difficult to answer all questions simply by network of neuroendocrine immune.