Inflammation and Related Phenomena 123 



and up to two hours later show no significant leucocyte emigration. 

 However, similar sections examined five hours after injection of 

 histamine show striking migration of polymorphs from small blood 

 vessels in the injected area. Even more remarkable is the observa- 

 tion that a similar delayed leucocyte emigration occurs after in- 

 jection of sterile isotonic saline which produces no demonstrable 

 increase in capillary permeability to protein whatsoever. 



It is clear that an explanation of this long latent period between 

 disturbance of the environment of small blood vessels and leucocyte 

 emigration must be sought in the affected tissues. Furthermore, the 

 sequence of injury leading to increased capillary permeability, e.g. 

 activation of plasma enzymes, breakdown of platelets, disruption 

 of mast cells seem too rapid to be responsible for the delayed onset of 

 leucocyte migration. 



The answer to this problem may lie in the observation that soon 

 after injection of histamine or saline, leucocytes may be seen adher- 

 ing to the inner surface of small vessels. It seems possible that these 

 white cells might slowly liberate a substance with the specific pro- 

 perty of inducing emigration of further leucocytes on a massive 

 scale. Such a process has been invoked to explain the liberation of 

 pyrogenic substances from leucocytes following injection of bac- 

 terial endotoxin. In fact, extracts of leucocytes from blood and 

 sterile exudates were found to contain a principle capable of in- 

 ducing large-scale emigration of leucocytes within thirty minutes 

 of their intradermal injection, a property not possessed by similar 

 extracts of other types of body cells. Preliminary experiments in- 

 dicate that a substance akin to that obtained from polymorph leuco- 

 cytes may be activated in serum by incubation with minced tissues. 



A substance with similar properties is present in the fluid por- 

 tion of sterile exudates produced by intraperitoneal infusion of 

 saline. In this instance the active principle might be derived from 

 both disrupted leucocytes and activated plasma. Another source 

 of the leucocyte emigration factor is rat skin when extracted several 

 hours after thermal injury when exudation of polymorphs due to 

 the burn is at its height. Here again, both sources may contribute 

 to the activity of the extract. Fractionation of these skin extracts re- 

 veals much of the activity to reside in the fraction associated chiefly 



