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Recombinant integrin CD11b A‐domain blocks polymorphonuclear cells recruitment and protects against skeletal muscle inflammatory injury in the rat
Author(s) -
Zerria K.,
Jerbi E.,
Hammami S.,
Maaroufi A.,
Boubaker S.,
Xiong J. P.,
Arnaout M. A.,
Fathallah D. M.
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02454.x
Subject(s) - integrin alpha m , cd18 , skeletal muscle , monoclonal antibody , recombinant dna , extravasation , receptor , pharmacology , biology , antibody , immunology , endocrinology , biochemistry , gene
Summary The β 2 integrin CD11b/CD18 (CR3) is a major adhesion receptor of neutrophils, normally utilized to fend off infections. This receptor contributes, however, to multiple forms of non‐infectious inflammatory injury when dysregulated as shown in gene knock‐outs and through the use of blocking monoclonal antibodies. The major ligand recognition site of CR3 has been mapped to the A‐domain in the CD11b subunit (CD11bA). The recombinant form of this domain exhibits a ligand binding profile similar to that of the holoreceptor. To assess the potential anti‐inflammatory activity of CD11bA as a competitive antagonist of CR3 in vivo , we assessed its effects on a developed animal model of traumatic skeletal muscle injury in the rat. Recombinant soluble rat CD11bA‐domain fused to glutathione‐S‐transferase (GST) was administered intravenously in a single dose at 1 mg/kg to nine groups of Wistar rats, five in each group, 30 min before inducing traumatic skeletal muscle injury. Control animals received either a function‐blocking anti‐CD11b/CD18 monoclonal antibody (1 mg/kg), non‐functional mutant forms of the CD11bA (D140GS/AGA, T209/A, D242/A), recombinant GST or buffer alone. In control animals, the wounded muscle showed oedema, erythrocyte extravasation and myonecrosis both within and outside the immediate wounded area (5–10 mm zone) and influx of neutrophils was detected 30 min post‐wound, followed by a second wave 3 hr later. Wild‐type CD11bA‐ or anti‐CD11b monoclonal antibody (mAb)‐treated rats showed a comparable and significant decrease in the number of infiltrating PMN (78 + 4%, n = 70 and 86 ± 2%, n = 50, respectively) and preservation of the muscular fibres outside the immediate zone of necrosis (75 + 4%, n = 70, 84 ± 1%, n = 50, respectively), compared to controls. These data demonstrate that CD11bA can be an effective tissue‐preserving agent in acute inflammatory muscular injury.