Generation of chemoattractant substances is believed to play an important role in the development and outcome of infectious and allergic processes. Recent studies have attracted attention to chemoattractant activities of substances such as LPC (lysophosphatidylcholine), HETEs (5-hydroxy or 12-hydroxy eicosatetraeonic acid) and leukotrienes which are derived from membrane phospholipids. Accordingly, we have initiated an immunological and biochemical investigation with the purpose of: (1) Conducting further studies of lysophosphatidylcholine, a newly recognized chemoattractant for lymphocytes, and (2) investigating a new aspect of complement-induced inflammation by assessing the role of complement proteins C5b-9 in the generation of LPC, HETEs, leukotrienes and, possibly, other chemoattractants from membrane phospholipids. With respect to LPC we want to determine what cell types respond to its attractant activity, what role it plays in vivo as a mediator of inflammation, what structural analogs of LPC exhibit chemoattractant activity, whether LPC is converted to other chemoattractants by responding cells, and whether LPC can induce formation of new chemoattractants including some arachidonate metabolites with known chemoattractant activity. With respect to complement, we want to determine what cell types produce chemoattractant factors when attacked by C5b-9 and to assess formation of LPC, HETEs, leukotrienes and, possibly, other chemoattractants. We expect that these efforts will expand knowledge of complement-induced inflammation beyond the well-known activities of complement fragments C3a, C4a, C5a, and C3b. We believe that activation of complement at tissue sites of infection, allergy and malignancy, is likely to lead to membrane damage which could activate membrane-associated phospholipase and other enzymes that are instrumental in producing chemoattractant phospholipid derivatives, including LPC.
