The cell activation model of hemocyte aggregation and adhesion in the California mussel, Mytilus californianus

Using hemocytes of the marine bivalve mollusc Mytilus californianus, cell aggregation (clump formation) and cell adhesion to the substratum have been exploited as indicators of hemocyte activation. Two intracellular signal transduction pathways, the cAMP pathway and the phospholipid/Ca{dollar}sp{lcub}++{rcub}{dollar} pathway, have been found to be involved in hemocyte activation. During activation intracellular levels of cAMP increase. Based on the synergistic and competitive effects of caffeine and adenosine or adenosine analogues on cell behavior, it is inferred that caffeine inhibits cell activation as a result of its binding to adenosine receptors. The putative adenosine receptor may initiate a cascade of reactions to activate adenylate cyclase and generate cAMP. The phospholipid/Ca{dollar}sp{lcub}++{rcub}{dollar} pathway was made evident by the activation ability of two protein kinase C activators, PMA and A23187. Both drugs overcame the inhibitory effects of caffeine on hemocyte activation. Extracellular calcium ions may also be critical to hemocyte activation, since the calcium channel blocker, verapamil, influenced hemocyte aggregation and adhesion, and 50 mM calcium could induce hemocyte adhesion in 10 mM caffeine. Cell surface carbohydrates also play a role in hemocyte adhesion and aggregation. These two cell behaviors have been found to be inhibited by NaIO{dollar}sb4{dollar} and N-acetyl-glucosaminidase, and promoted by neuraminidase and hyaluronidase. In addition, cytoskeleton assembly is also involved in these two cell activities.; Although some evidence implies indirectly that hemocyte aggregation and adhesion are distinct behaviors, the adhesion molecules putatively involved remain to be identified, so cannot be relied upon to distinguish these two cell behaviors. However, these two cell events likely utilize the same or very similar activation pathways. Not only do both behaviors always occur simultaneously, but their inhibition and enhancement were effected by the same reagents in most cases. In addition, as demonstrated in sponge cell aggregation or myoblast aggregation, Mytilus hemocyte aggregation appears to be a two-step process that advances through weak aggregation to cohesive aggregation, and which is modulated by temperature and dependent on divalent cations and metabolic energy.