Mobilization of defensive cells in inflammatory tissue.

The present poverty of the classical techniques of morbid anatomy is nowhere better illustrated than in the study of inflammation. The essential characteristics of the emigration of polymorphonuclear leucocytes from vessels were described by the middle of the 19th century (1-3); and the association of monocytes with the lesions of leprosy, typhoid, and tuberculosis was described at about the same time (4-6). Chemotaxis of polymorphonuclear leucocytes was described by Leber in 1888 (7). In 1892 Metchnikoff delivered the classical lectures in which the phagocytic role of polymorphonuclear leucocytes and monocytes was elucidated (8). Collections of eosinophilic leucocytes in the tissues in certain pathological conditions had been described by the 1890's (912), and by 1901 the general doctrine had already been established that lymphocytes accumulated in the tissues wherever there was prolonged cellular disintegration (13). Descriptions of lymphocytes in various forms of chronic inflammation had, of course, been given earlier (14-16). The following features of inflammation were therefore well known by the beginning of the century: a. Polymorphonuclear leucocytes adhered to the walls of inflamed blood vessels and emigrated through these walls into the tissues. b. Polymorphonuclear leucocytes were attracted chemotactically toward many bacteria and were able to phagocytize and digest some of them. c. Certain bacterial lesions were characterized by the accumulation of large numbers of mononuclear cells (the macrophages of Metchnikoff), and such cells were also seen during wound healing and in many forms of chronic inflammation. d. The mononuclear cells showed phagocytosis of bacteria and also of tissue debris. e. Eosinophile leucocytes collected in the tissues in a variety of parasitic infestations and also in certain other conditions such as bronchial asthma. f. Cells indistinguishable from lymphocytes collected in and around chronic inflammatory lesions, certain tumors, and transplanted tissues. The astonishing thing about this list is that it can, with very little addition, stand as a summary of contemporary knowledge of the role of defensive cells in inflammation. We have not yet determined: a. Whether there are any specific chemical substances responsible for the mobilization of the polymorphonuclear leucocytes. b. Whether monocytes emigrate from the vessels in the same way and at the same time as polymorphonuclear leucocytes or whether the emigration of monocytes is provoked by physical or chemical stimuli different from those which provoke the emigration of polymorphonuclear leucocytes. c. The mechanism of eosinophile accumulation. d. The mechanism of lymphocyte accumulation. These four unresolved questions and some aspects of the information available about each of them will be discussed in this review. Certain possibilities for experiment will also be suggested. Of course, no one can really know whether an experimental approach is actually feasible until it is tried, but since our experimental record in the field of inflammation during the last 50 years is, on the whole, a poor one there may be some excuse for rashness.