Complement activation and membrane lipids in lung vascular injury.

Area of Science:

• Immunology
• Physiology

Background:

• Intravascular complement activation, specifically C5a, triggers rapid neutropenia and transient hypotension in animal models.
• Hematologic changes suggest the involvement of polymorphonuclear leukocytes (PMN) and mediators like vasoamines and prostanoids.

Purpose of the Study:

• To investigate the mechanisms underlying C5a-induced hypotension and neutropenia in rabbits.
• To determine the roles of prostanoids, histamine, and PMNs in the observed hemodynamic and hematologic responses.

Main Methods:

• Administered purified C5a to rabbits and monitored hemodynamic parameters (CVP, CO) and hematologic changes (neutropenia).
• Utilized indomethacin and H1/H2 histamine receptor antagonists to assess the involvement of prostanoids and histamine.
• Investigated the effect of pre-existing neutropenia (induced by nitrogen mustard) on the C5a response.

Main Results:

• C5a administration led to hypotension, increased central venous pressure, decreased cardiac output, elevated plasma prostanoid levels, and neutropenia.
• Indomethacin blocked hypotension but not neutropenia, indicating prostanoids mediate hypotension.
• H2 receptor antagonists reduced hypotension and prostanoid release, suggesting histamine's role.
• Pre-existing neutropenia did not alter the C5a-induced hypotension or prostanoid release.
• Elevated prostacyclin (PGI2) and thromboxane B2 (TXB2) levels were observed, with TXB2-dependent pulmonary vasoconstriction contributing to hypotension.

Conclusions:

• C5a-induced hypotension in rabbits is significantly mediated by prostanoids, particularly thromboxane-dependent pulmonary vasoconstriction.
• Histamine, via H2 receptors, may contribute to the C5a response.
• Neutropenia is a parallel event to hypotension and appears to have minimal influence on the hemodynamic response.