Products of unusual microtubule dynamics in monocyte-derived giant cells. An immunohistochemical study

Abstract

We have studied asteroid bodies (ABs) of multinucleated giant cells (MGCs) in a series of sarcoid and foreign body granulomas with a standard streptavidin-biotin peroxidase technique, using commercial antibodies against collagen, vimentin and tubulin on routinely processed tissue as well as, in one case, on fresh frozen sections (FS). Our findings clearly indicate that ABs are products of the microtubule (MT) system and lack collagen. The tubulin in them stains in fresh FS but is «masked» in formalin-fixed tissue. It can be fully «unmasked» by dephosphorylation and partially by trypsinization. Compared to single microtubule organizing centers (MTOCs) in mononuclear cells serving as interna1 controls, ABs are obvious replicas of centrosome-nucleated MT assemblies from which they differ principally by the disproportionate size of their components and by the invariable vacuolation of the surrounding cytoplasm. Relying on bits of relevant information gleaned from the literature, our observations support the following preliminary conclusions: 1) spokes are massive bundles of MTs nch in tyrosinated a-tubulin coassembled in phosphorylated linkages with yet unidentified microtubule associated proteins (MAPs) and probably microfilament proteins; cores are masses of pericentriolar material including amorphous tubulins, MAPs, phosphoproteins and phospholipids; 2) their size, at least in some ABs, appears to indicate the presence of overlapping centrosome-nucleated MTOCs which in monocyte-derived MGCs are known to be multiple; 3) the cytoplasmic vacuolations around them reflect a collapse and retraction of intermediate filaments (IFs), indicating substantial ongoing MT depolymerization with disruption of MT-IF interactions; 4) ABs are products of unusual MTOC dynamics characterized by simultaneous MT assembly and depolymerization; such a phenomenon, temed «microtubule catastrophec, has been recognized in vitro with centrosome-nucleated MT assemblies under conditions of low tubulin concentrations.