428 V. BLOOD LIPIDS 



Heart, lung 

 Reaction a: [ 



tissue factor 



fraction IV-1 > clearing factor 



+ heparin 



Reaction b: 



clearing factor 



turbid lipoprotein > decreased turbidity 



(high 5/) co-protein (lower 5/ ) 



In a later report, Brown and Kauffman 446 reported that the in vivo adminis- 

 tration of heparin to a variety of animals causes the production of a plasma 

 enzyme, termed the "clearing factor." This protein, in the presence of a 

 second plasma protein, or "co-protein," brings about a decrease in the 

 turbidity of lipemic plasmas, a decrease in the ultracentrifugation flotation 

 rates of low density lipoproteins, and a concomitant production of a- 

 lipoprotein molecules. The lipemia clearing factor can be produced 

 in vitro when heparin is incubated with rat pylorus; the activity is stable 

 for three months, in contrast to the instability of preparations obtained 

 when rat heart or lung extracts are employed. 



Only injected heparin will initiate the production of the clearing factor. 

 Thus, Levy and Swank 447 reported that conditions such as shock, due to 

 anaphylaxis or to the injection of certain histamine liberators, which is 

 known to bring about the appearance of native heparin in the blood, does 

 not necessarily coincide with the clearing of a lipemia. Heparin does not 

 inhibit cortisone-induced lipemia or hypercholesterolemia in the rabbit; 

 in fact, Constantinides et a?. 448 reported that it even tended to increase it. 



The most important effect of heparin is on the formed fat particles. 

 Fidlar and Jaques 449 suggested that heparin reduces the number of blood- 

 platelets, in a manner similar to its effect upon the dispersion of the chylo- 

 microns. It presumably combines with the lipoprotein complex or splits 

 off the lipid portion and becomes itself bound with the protein moiety. 450 

 Snellman et al. ibl isolated a compound present in tissue mast cell cyto- 

 plasm containing heparin associated with a polypeptide and a lipid residue. 

 All three components must be present to produce the antithrombin effect. 

 It is not known whether or not this is similar to the clearing factor. Swank 

 and Levy 452 also postulate that the mechanism by which heparin lowers 



446 R. K. Brown and D. L. Kauffman, Federation Proc, 12, 183-184 (1953). 



447 S. W. Levy and R. L. Swank, Proc. Soc. Exptl Biol Med,, 82, 553-556 (1953). 



448 P. Constantinides, G. Szasz, and M. Darrach, XIX Intern. Physiol. Congress, 

 Montreal (Aug.-Sept., 1953), Abst. 277-278. 



449 E. Fidlar and L. B. Jaques, J. Lab. Clin. Med., S3, 1410-1423 (1948). 



460 E. Chargaff, Advances in Protein Chem., 1, 1-24 (1944). 



461 O. Snellman, B. Sylven, and C. Julen, Biochim. etBiophys. Acta, 7, 98-109 (1951). 



462 R. L. Swank and S. W. Levy, Am. J. Physiol, 171, 208-217 (1952). 



