Use of a bovine model to study the role of adhesion molecule CD11/CD18 in hemodialysis-induced neutropenia.
The early neutropenia that occurs with cellulose-based dialysis membranes is believed to result from a cascade of immune events: complement activation, engagement of leukocyte adhesion molecules, cytokine release, and leukocyte sequestration. The beta2 integrin CR3 (CD11b/CD18) is upregulated during hemodialysis, binds complement factor iC3b, and mediates leukocyte adhesion to endothelium and leukoaggregation. Despite being invoked in dialysis-induced neutropenia, there is no direct evidence of a role for CD11b/CD18 in the neutropenia. A unique animal model of beta2-integrin deficiency was discovered in calves experiencing recurrent infections and a paucity of leukocytes in infected tissue. We hypothesized that beta2 integrins mediate the neutropenia of dialysis and directly tested this hypothesis using beta2-integrin-deficient calves. Two 3-month old beta2-integrin-deficient and two age-matched Holstein calves were dialyzed using cuprophane dialyzers. Beta2-integrin-deficient calves had less than 2% of normal neutrophil CD18 expression by flow cytometry. Normal calves had a marked decrease in circulating neutrophils (P < 0.05) to 15% of normal 15 minutes into dialysis (total, four treatments), as well as a decrease in monocytes to 39% (P < 0.05) and lymphocytes to 58% (P < 0.05). CD18-deficient calves had an attenuated decrease in neutrophils (65%; P = not significant), monocytes (78%; P = not significant), and lymphocytes (105%; P = not significant) at 15 minutes. These data, although obtained in a small sample, show that a bovine model can be used to study the early neutropenia of dialysis. These data also suggest that a direct role of beta2 integrins may be occurring in this process.
Rabb
Hamid
H
Nephrology Division, Johns Hopkins University Hospital, Baltimore, MD, USA. hrabb1@jhmi.edu
Chandran
Prem K G
PK
Arnaout
M Amin
MA
Kehrli
Marcus E
ME
D000704:Analysis of Variance; D000818:Animals; D018845:CD11 Antigens / Q000032:analysis / Q000502:physiology*; D018821:CD18 Antigens / Q000032:analysis / Q000502:physiology*; D002417:Cattle; D005434:Flow Cytometry; D007958:Leukocyte Count; D008567:Membranes, Artificial; D023421:Models, Animal; D009503:Neutropenia / Q000209:etiology* / Q000276:immunology*; D006435:Renal Dialysis / Q000009:adverse effects* / Q000295:instrumentation; D018401:Sample Size
D018845:CD11 Antigens; D018821:CD18 Antigens; D008567:Membranes, Artificial