Stereospecific chemoattraction of lymphoblastic cells by gradients of lysophosphatidylcholine.

Abstract

Human plasma contains chemoattractant activity for cultured cells from the mouse thymic lymphoma 6C3HED and also for lymphoblasts from concanavalin A-stimulated mouse spleen cells. A major portion of the attractant activity for both cell types could be attributed to plasma lysophosphatidylcholine. Studies on synthetic lysophosphatides showed that polar head group structure, acyl chain length, and stereochemical configuration are important determinants for attractant activity.Substances that cause the accumulation of lymphoid cells in sites of inflammation or control the migration of these cells through the tissues of lymphoid organs may play important roles in immune responses (1). Oriented migration (chemotaxis), increased random motility (chemokinesis), or other cellular mechanisms may cause cells to migrate toward the source of a chemoattractant gradient. t Many different substances have been reported to be chemoattractants for lymphoid cells. Among these are plasma and altered components of plasma (2), a proteolytic fragment of IgG (3), lymphokine-containing supernates from mixed lymphocyte cultures (4), lectins that are mitogenic for lymphocytes (5), a 10,500-dalton factor from immune calf thymus (6), specific antigens (2), arachidonic acid and its metabolites (7,8), and bacterial components, including staphylococcal protein A (5).In the course of studies on the attractant activity of plasma, we discovered that plasma could attract not only concanavalin A (Con A)-stimulated spleen lymphocytes but also neoplastic cells from the cultured thymic lymphoma 6C3HED. Both cell types responded similarly to plasma lipid extract and lipid fractions. Isolation and characterization of the active principle led us to conclude that much of the attractant activity in plasma could be accounted for by lysophosphatidylcholine (LPtdCho). To study the mechanism by which LPtdCho exerts its effect on lymphoid cells, we set out to define the structural requirements for molecules with attractant activity.MATERIALS AND METHODS Solvents. Organic solvents purchased from Burdick-Jackson Laboratories (Muskegon, MI) were used without further purification.Media. Cell cultures were maintained in medium A [RPMI-1640 medium supplemented with 10% (vol/vol) heat-inactivated fetal calfserum, 2 mM L-glutamine, and 100 units ofpenicillin, and 100 Mug ofstreptomycin per ml]. Medium B [minimal essential medium with Earle's salts supplemented with 0.5% bovine serum albumin (Cohn fraction V; Sigma), 70 mM sodium Hepes (pH 7.5), and 100 units ofpenicillin, and 100 Ag ofstreptomycin per ml] was used for migration assays.Migration Assay. Cell migration under agarose gels was assayed essentially as described by Nelson et al. (9). Six round glass coverslips were placed in hexagonal array in 60 X 15 mm plastic culture dishes. Four milliliters of a mixture of 5 vol of medium B and 1 vol of 80 mM sodium Hepes, pH 7.5/5% Litex LSA agarose (Accurate, Hicksville, NY) was added over the coverslips in each dish. Three wells were cut in the gel over each c...

A Hybrid Agent-Based Model of Chemotaxis

“…The distortion then slowly decreases, indicating increasing spread along the y axis due to gradient created at the edge of the migration shape. The cells spread rather than move with a narrow front, hence our results differ from the illustration from [10] but closer to the photo in [19] (see Fig. 2).…”

T cell chemotaxis to lysophosphatidylcholine through the G2A receptor

“…A chemotactic role for LPC has been previously suggested (19,20), but the receptor involved has not been identified. To determine the requirement for endogenous expression of G2A in LPC-induced chemotaxis, we examined the migration of DO11.10 cells toward this LP in a transwell-based assay.…”

Generation of lyso-phospholipids from surfactant in acute lung injury is mediated by type-II phospholipase A2 and inhibited by a direct surfactant protein A-phospholipase A2 protein interaction.

“…Furthermore, among lyso-phospholipid subclasses, lyso-PC is the most effective in potentiating the diacylglycerol-induced activation of particular calcium-dependent protein kinase C isoforms, suggesting a role in cell activation (6,7). Finally, lyso-PC exhibits chemotactic activities toward lymphoid (8,9) and mononuclear cells (10) and induces the expression of vascular cell adhesion molecules and intercellular adhesion molecules in endothelial cells (11,12), suggesting a role in cell recruitment during inflammation.…”