Expression and distribution of cell-membrane complement regulatory glycoproteins along the human respiratory tract.
Complement in the human respiratory tract protects the host from invading microorganisms and from other inhaled insults. However, complement may also lyse the host's respiratory tract cells, leading to tissue injury. In many extrapulmonic tissues, cells express cell-membrane complement regulatory glycoproteins that protect the cells from complement-induced lysis. To determine whether these glycoproteins are expressed in human respiratory tract tissue, we studied tissue biopsies of healthy and diseased human respiratory tract from nose to alveoli for the presence of four cell-membrane complement regulatory glycoproteins (membrane cofactor protein [MCP], decay-accelerating factor [DAF], CD59, and complement receptor type 1 [CR1]) using an immunoperoxidase technique. In addition, to establish a model for in vitro studies of these glycoproteins in respiratory cells, we studied whether they are expressed in cultured nasal epithelial cells, using the same technique. Altogether, 26 tissue specimens from 22 patients were studied. We found that normal human respiratory tract from nose to alveoli express MCP, DAF, and CD59, but not CR1, and that this expression increases in inflammation and in lung cancer. In addition, expression in nasal epithelial cells is retained under cell culture conditions. These findings suggest that human respiratory tract tissue may regulate complement activation on its surface in order to avoid self-injury. We propose that imbalances in the mechanism that regulates cell-membrane complement may predispose the respiratory tract to tissue injury and disease, and that iatrogenic modulation of such imbalances may help to prevent these adverse consequences.
Varsano
S
S
Department of Pulmonary Medicine, Sapir Medical Center, Meir General Hospital, Kfar Sava, Israel.
Frolkis
I
I
Ophir
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D018958:CD55 Antigens; D018957:CD59 Antigens; D002478:Cells, Cultured; D003169:Complement Inactivator Proteins / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011951:Receptors, Complement / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology; D012140:Respiratory Tract Diseases / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D001798:Blood Proteins; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D003165:Complement System Proteins