Biphasic regulation of macrophage attachment by activators of cyclic adenosine monophosphate‐dependent kinase and protein kinase C

Abstract

A method is described that enabled us to study the adhesiveness of J-774 murine macrophages. Cell attachment was stimulated by activators of kinase C (i.e., phorbol esters) as well as kinase A (cyclic adenosine monophosphate; cAMP). This novel effect of cAMP was observed when its levels were increased via receptor triggering (prostaglandin E1, beta-adrenergic agonists), activation of Ns (cholera toxin), or inhibition of phosphodiesterase (Ro 20-1724) or when the kinase was directly activated by Br8-cAMP. The simultaneous treatment with kinase A and kinase C activators at the time of attachment resulted in a partially additive response. On the other hand, preincubation of the cells in suspension with one of the activators rendered them refractory to subsequent stimulation at the onset of the adhesion assay, whatever agent was used. Such a refractoriness was also observed in cells preincubated with oleoyl-acetyl-glycerol (OAG). On the other hand, when added at the time of attachment, this near-physiological activator of kinase C evoked a biphasic response: the early stimulation of cell attachment was followed by an accelerated rate of "detachment." In conclusion, kinase C and kinase A play a role in the sequence of events leading to cell adhesion. The cross desensitization observed is distal and takes place at or beyond the kinase step.

Essential differences in cholesteryl ester metabolism between human monocyte-derived and J774 macrophages. Evidence against the presence of hormone-sensitive lipase in human macrophages.

“…Thus, whereas it inhibits adherence of RAW264 cells, 4 " it stimulates adherence of J774 macrophages. 41 cAMP induces depolymerization of actin filaments in guinea pig peritoneal macrophages, 42 and in human monocyte-derived macrophages it interferes with the assembly and stability of microtubules. 41 Therefore, impairment of the cellular cytoskeleton by cAMP may have caused the cell detachment observed in the present study with human macrophages.…”

“…41 cAMP induces depolymerization of actin filaments in guinea pig peritoneal macrophages, 42 and in human monocyte-derived macrophages it interferes with the assembly and stability of microtubules. 41 Therefore, impairment of the cellular cytoskeleton by cAMP may have caused the cell detachment observed in the present study with human macrophages. Since cell viability was unaffected by cAMP, studies on its effects on cholesteryl ester metabolism were feasible, although a special experimental design had to be adopted to prevent the loss of cellular material.…”

Sympathetic modulation of immunity: Relevance to disease

“…Macrophage adhesion is augmented following β-AR agonist treatment [251]; however, the β 2 -AR agonist treatment suppresses phagocytic activity of murine peritoneal macrophages [176,252]. Similarly, α-AR agonist treatment inhibits phagocytosis [176,253] by enhancing Ca 2+ -dependent K + channels activation in macrophages [177].…”

Modulation of human neutrophil function in vitro by gastrin

“…This has been found with several neuropeptides such as GRP (De la Fuente et al 1991) and VIP (De la Fuente et al 1993Í), 1994/)) which decreased cAMP levels in murine peritoneal macrophages and increased the phago¬ cytic process. Adherence was the only function increased by gastrin and this could be due to the fact that this neutrophil function is mediated by the activation of cAMP-dependent kinase (Isaad et al 1989, Sung et al 1991.…”