IDENTIFICATION OF HEMATOPOIETIC BIGLYCAN IN HYPERPLASTIC THYMUS ASSOCIATED WITH MYASTHENIA-GRAVIS

Generally biglycan, a small proteoglycan, has been thought to play a r ole as an extracellular matrix and/or a reservoir for other factors, s uch as TGF-beta and collagens. Recently, we have found that a soluble 100 kDa biglycan, produced from the rat thymic myoid cells and the bra in glial cells, predominantly stimulates growth and differentiation of monocytic Lineage cells from various lymphatic organs, including micr oglias. In the present study, we attempted to identify biological sign ificance of the corresponding molecules in human, using five myastheni c thymuses (three with hyperplasia and two with thymoma) that had been surgically removed for therapeutic purpose. With immunohistochemistry , many biglycan positive cells were detected in the germinal center of the three hyperplastic thymuses, but not in the two thymuses associat ed with lymphocytic thymoma. Biglycan purified from the hyperplastic t hymuses by an immunoaffinity column was found as a monomer with appare nt molecular size of 95-100 kDa and self associated oligomers of great er than 201 kDa. The purified biglycan markedly stimulated the growth and differentiation of monocytic cells from haemopoietic stem cells of the rat bone marrow. These results suggest that particular cells, whi ch produce haemopoietic biglycan, play significant roles in generation and maintenance of the hyperplastic changes associated with myastheni a gravis. (C) 1998 Elsevier Science B.V. All rights reserved.