[Frontiers in Bioscience 3, d973-984, September 1, 1998] |
EVOLUTION AND PHYLOGENY OF DEFENSE MOLECULES ASSOCIATED WITH INNATE IMMUNITY IN HORSESHOE CRAB
Sadaaki Iwanaga and Shun-ichiro Kawabata
Department of Biology, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan
Received 7/13/98 Accepted 8/21/98
Innate immunity requires adequately specific biosensors, in which they should react with various epitopes that consist of slightly different structures on a variety of pathogens, but must distinguish "self" and "non-self" epitopes (86,87). Examples of such specificity can be found in the activation of the horseshoe crab clotting factors, factor C and factor G, both of which are sensitive to major cell wall components, such as LPS and (1,3)-b-glucan. The clotting system initiated by pathogens plays important roles not only in hemostasis, but also in the defense to immobilize invaders. The clear difference between the vertebrate and horseshoe crab clotting systems is that all the clotting factors of horseshoe crab exist in the circulating hemocytes, not in blood plasma as seen in vertebrate animals. Especially, many L-granules found in the horseshoe crab hemocytes contain all the clotting factors essential for hemolymph coagulation. On the other hand, antimicrobial substances including tachyplesins, tachycitin, tachystatins, and big defensin, which kill invaders directly or synergistically, are stored in S-granules. In response to foreign organisms, the contents of both granule populations are released into hemolymph via exocytosis, where they work together to immobilize and kill invaders. The hemolymph plasma containing C-reactive proteins (89,93) and a2-macroglobulin (88,90-92) also exhibits cytolytic activity against foreign cells, like the mammalian complement system. These cellular and humoral defense systems covering the innate immunity in concert, defend effectively horseshoe crab from invading microbes (94). We would finally emphasize that the defense molecules actively at work in innate immunity are structurally and functionally very similar between horseshoe crab and vertebrate animals. There is clearly still much to be learned about the origins of defense molecules derived from invertebrate animals.