180 PHAGOCYTOSIS 



was first clearly demonstrated by Leber 1 in 1879. This writer ob- 

 served that in keratitis leukocytes invaded the avascular cornea 

 from the distant vessels, not in an irregular manner, but direct to the 

 point of infection, where they accumulated. As dead cultures of 

 staphylococci produced a similar although a less pronounced accumu- 

 lation of leukocytes, Leber sought the chemotactic substance in their 

 bodies, and isolated a crystalline, heat-resisting substance phogosin 

 which attracted leukocytes in the tissues. 



Since these fundamental studies were made many other investiga- 

 tions, with various chemical substances of many different origins, have 

 been undertaken upon leukocytes, amebae, ciliata, and plasmodial forms, 

 indicating that chemical substances are mainly concerned in exerting 

 either a positive or a negative chemotactic influence. 



Experimental evidence tends to show that cells respond to stimuli 

 of various kinds chiefly through the effect of these stimuli upon surface 

 tension: if they decrease the surface tension, the cell goes forward; if 

 they increase the tension, the cell recedes. 



The behavior of leukocytes in inflammation may be explained on 

 these purely physical grounds. At the site of cell injury or infection 

 chemical substances are produced that tend to lower the surface tension 

 of leukocytes and thus exert a positive chemotactic influence. These 

 chemical stimuli are transmitted by the body-fluids to the nearest cap- 

 illaries, where they enter through the vessel-wall and come in relation 

 with the slowly moving peripheral leukocytes. The leukocytes will be 

 brought into touch by the chemotactic substances most largely on the 

 side from which the substances diffuse; accordingly, the surface tension 

 being least nearest the stomata in the capillary wall, this results in the 

 formation of pseudopodia, and motion in this direction, dragging the 

 nucleus along in an apparently passive manner. Those cells, therefore, 

 containing most of the mobile cytoplasm, such as the polynuclear leuko- 

 cytes, are chiefly affected in these processes; those containing little 

 cytoplasm and a relatively large and dense nucleus, such as the lympho- 

 cytes, are affected primarily to a much less extent. 



Once outside of the vessel-wall, the leukocytes tend to move toward 

 the focus from which the chemotactic substance comes. If the leuko- 

 cyte meets a substance that greatly lowers its surface tension, it will flow 

 around the object and inclose it, this constituting phagocytosis. The 

 toxins of the ingested bacteria may kill the cell, or so equalize surface 

 tension that movement ceases. Otherwise the leukocytes tend to move 

 1 Fortschritte der Med., 1888, 6, 460. 



