Arachidonate cyclooxygenase metabolites as mediators of complement-initiated lung injury.

The pulmonary effects of intravascular complement activation can be divided into those that are initial events of activation and those that depend on the duration of intravascular activation. Pulmonary leukostasis is both an initial event and one that persists as long as intravascular complement activation is ongoing. This event is independent of synthesis and release of cyclooxygenase products of arachidonic acid. Initial events include synthesis and release of thromboxane and development of pulmonary hypertension and hypoxemia. Cyclooxygenase products are mediators of these initial pathophysiological events in part or in total. Complement-initiated increases in lung microvascular permeability are dependent on the duration of intravascular complement activation. Activation must be either prolonged or repeated to produce significant microvascular injury. This process is unrelated to synthesis and release of cyclooxygenase products, but is related to release of toxic oxygen metabolites.