In Vivo Recruitment of Neutrophils: Consistent Requirements for L-Arginine and Variable Requirements for Complement and Adhesion Molecules

Abstract

The current studies examined the mechanisms of neutrophil recruitment into the rat peritoneal cavity following injection of glycogen and into rat lungs following alveolar deposition of IgA immune complexes or airway instillation of phorbol ester (PMA). Unexpectedly, in each model a requirement for L-arginine for neutrophil recruitment was demonstrated, since administration of the L-arginine analogue, N^G-monomethyl L-arginine acetate (L-NMA), greatly reduced neutrophil accumulation as assessed by quantitation of neutrophils in peritoneal exudates and bronchoalveolar lavage fluids, and by lung myeloperoxidase content. In the case of IgA immune complex deposition, lung recruitment of neutrophils was also suppressed by soluble recombinant human complement receptor-1 (sCR1) and antibody to CD18 but not by antibody to E-selectin. In contrast, neutrophil accumulation following airway instillation of PMA exhibited, surprisingly, no requirement for complement but requirements for both E-selectin and CD18. These data demonstrate variable requirements for complement, E-selectin and CD18 but a consistent requirement for L-arginine for neutrophil recruitment. These findings provide evidence suggesting that L-arginine or its derivatives regulate neutrophil recruitment.