{'fraction_non_alphanumeric': 0.037108125399872044, 'fraction_numerical': 0.023032629558541268, 'mean_word_length': 5.436213991769547, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Regulation of Cytosolic Phospholipase A2 Activity in Macrophages Stimulated with Receptor-recognized Forms of α2-Macroglobulin

Macrophages exposed to receptor-recognized forms of α2-macroglobulin (α2M*) demonstrate increased DNA synthesis and cell division. In the current study, we have probed the role of cytosolic phospholipase A2 (cPLA2) activity in the cellular response to α2M*. Ligation of the α2M* signaling receptor by α2M*, or its receptor binding fragment, increased cPLA2 activity 2–3-fold in a concentration and time-dependent manner. This activation required a pertussis toxin-insensitive G protein. Cellular binding of α2M* also induced transient translocation of cPLA2 activity to nuclei and membrane fractions. Inhibition of protein kinase C activity or chelation of Ca2+ inhibited α2M*-induced increased cPLA2 activity. Binding of α2M* to macrophages, moreover, increased phosphorylation of MEK 1/2, ERK 1/2, p38 MAPK, and JNK. Incubation of macrophages with inhibitors of MEK 1/2 or p38 MAPK before stimulation with α2M* profoundly decreased phosphorylation of MAPKs, blocking cPLA2 activation. α2M*-induced increase in [3H]thymidine uptake and cell proliferation was completely abolished if activation of cPLA2 was prevented. The response of macrophages to α2M* requires transcription factors nuclear factor κB, and cAMP-responsive element-binding protein as well as expression of the proto-oncogenes c-fos and c-myc. These studies indicate that the activation of cPLA2 plays a crucial role in α2M*-induced mitogenesis and cell proliferation.