ant ▁in ▁t issue ▁flu ids . ▁ ▁This ▁is ▁referred ▁to ▁as ▁the ▁S 1 P ▁gradient , ▁which ▁seems ▁to ▁have ▁bi ological ▁significance ▁in ▁imm une ▁cell ▁tra ff ick ing . ▁ ▁Origin ally ▁thought ▁as ▁an ▁int rac ell ular ▁second ▁mess enger , ▁it ▁was ▁discovered ▁to ▁be ▁an ▁ext rac ell ular ▁lig and ▁for ▁G ▁protein - cou ple d ▁re ceptor ▁S 1 PR 1 ▁in ▁ 1 9 9 8 . ▁It ▁is ▁now ▁known ▁that ▁S 1 P ▁re cept ors ▁are ▁members ▁of ▁the ▁l ys oph osph ol ip id ▁re ceptor ▁family . ▁There ▁are ▁five ▁described ▁to ▁date . ▁Most ▁of ▁the ▁bi ological ▁effects ▁of ▁S 1 P ▁are ▁medi ated ▁by ▁signal ing ▁through ▁the ▁cell ▁surface ▁re cept ors . ▁ ▁Although ▁S 1 P ▁is ▁of ▁importance ▁in ▁the ▁entire ▁human ▁body , ▁it ▁is ▁a ▁major ▁reg ulator ▁of ▁v asc ular ▁and ▁imm une ▁systems . ▁ ▁In ▁addition , ▁it ▁might ▁be ▁ ▁relevant ▁in ▁the ▁skin . ▁In ▁the ▁v asc ular ▁system , ▁S 1 P ▁regul ates ▁ang i ogen esis , ▁v asc ular ▁stability , ▁and ▁per me ability . ▁In ▁the ▁imm une ▁system , ▁it ▁is ▁now ▁recognized ▁as ▁a ▁major ▁reg ulator ▁of ▁tra ff ick ing ▁of ▁T - ▁and ▁B - cell s . ▁S 1 P ▁interaction ▁with ▁its ▁re ceptor ▁S 1 PR 1 ▁is ▁needed ▁for ▁the ▁e