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β 2 Integrin independent neutrophil recruitment and injury in anti‐GBM glomerulonephritis in rabbits
Author(s) -
TIPPING P. G.,
CORNTHWAITE L. J.,
HOLDSWORTH S. R.
Publication year - 1994
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1994.71
Subject(s) - glomerulonephritis , integrin , neutrophile , immunology , cancer research , medicine , inflammation , receptor , kidney
Summary The role of the β2 integrin cell adhesion molecules (CAM) in directing neutrophil accumulation and injury in acute anti‐glomerular basement membrane antibody induced glomerulonephritis (anti‐GBM GN) was assessed in rabbits by in vivo inhibition of CD 18 dependent neutrophil/endothelial cell interactions using a monoclonal anti‐CD 18 antibody. Rabbits given horse anti‐rabbit GBM antibody developed significant glomerular neutrophil influx (2.9 ± 0.1 neutrophils per glomerular cross‐section [c/gcs], normal 0.1 ± 0.1 c/gcs, P = 0.002) and proteinuria (1389 ± 257 mg/16 h, normal 15± 4mg/16 h, P = 0.0015) after 16 h. Rabbits rendered neutropenic (< 500 neutrophils/μL) by mustine hydrochloride, or complement depleted by cobra venom factor, did not develop glomerular neutrophil accumulation and had markedly reduced proteinuria after anti‐GBM antibody, demonstrating complement‐induced neutrophil recruitment is a major mechanism of glomerular injury in this model. Anti‐CD 18 antibody treatment of rabbits developing anti‐GBM GN abrogated dermal neutrophil influx in response to intradermal injection of fMLP and zymosan activated serum. Treated rabbits achieved levels of anti‐CD 18 antibody in their serum which saturated the binding sites on rabbit neutrophils in vitro , and their circulating neutrophils had saturated anti‐CD 18 antibody binding in vivo. However, glomerular neutrophil influx (3.5 ± 0.4 c/gcs) and proteinuria (1210 ± 428 mg/16 h) were both unaffected. Thus, in this model of antibody‐initiated complement and neutrophil‐dependent glomerular injury, in which neutrophil transmigration across the endothelium is not required, effective functional inhibition of β 2 integrin CAM in vivo did not reduce glomerular injury or glomerular neutrophil influx. These studies demonstrate that β 2 integrin CAM are not a requirement for neutrophil accumulation and glomerular injury in anti‐GBM GN in rabbits.