Requirement and role of C5a in acute lung inflammatory injury in rats.
The complement activation product, C5a, may play a key role in the acute inflammatory response. Polyclonal antibody to rat C5a was used to define the requirements for C5a in neutrophil-dependent inflammatory lung injury after systemic activation of complement by cobra venom factor (CVF) or after intrapulmonary deposition of IgG immune complexes. In the CVF model, intravenous infusion (but not intratracheal instillation) of anti-C5a produced a dose-dependent reduction in lung permeability and in lung content of myeloperoxidase. In C6-deficient rats, CVF infusion caused the same level of lung injury (measured by leak of 125I-albumin) as found in C6-sufficient rats. In the IgG immune complex model of lung injury, anti-C5a administered intratracheally (but not intravenously) reduced in a dose-dependent manner both the increase in lung vascular permeability as well as the buildup of lung myeloperoxidase. Treatment with anti-C5a greatly suppressed upregulation of lung vascular intercellular adhesion molecule-1 (ICAM-1). This was correlated with a substantial drop in levels of TNFalpha in bronchoalveolar fluids. These data demonstrate the requirement for C5a in the two models of injury. In the IgG immune complex model, C5a is required for the full production of TNFalpha and the corresponding upregulation of lung vascular ICAM-1.
Mulligan
M S
MS
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Schmid
E
E
Beck-Schimmer
B
B
Till
G O
GO
Friedl
H P
HP
Brauer
R B
RB
Hugli
T E
TE
Miyasaka
M
M
Warner
R L
RL
Johnson
K J
KJ
Ward
P A
PA
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002634:Chemotaxis, Leukocyte; D003167:Complement Activation; D015936:Complement C5a / Q000276:immunology / Q000502:physiology*; D004546:Elapid Venoms / Q000008:administration & dosage / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007322:Instillation, Drug; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D004546:Elapid Venoms; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; C016310:cobra venom factor; D018799:Intercellular Adhesion Molecule-1; D015936:Complement C5a; D009195:Peroxidase