Plasminogen: A Brief Introduction into Its Biochemistry and Function

Abstract

Human plasminogen is a β-globulin (2 % carbohydrate, molecular weight 90 KD), which in its native form has NH₂-terminal glutamic acid (Glu-plasminogen) whose primary structure is known (31, 37, 38). From human plasma plasminogen can easily be isolated by affinity chromatography techniques (10, 25, and Table 1). Plasminogen is synthesized in many organs. The production site of the zymogen may be the liver (21), the eosinophiles (3) or the kindney (15). The plasma-plasminogen level is low in newborns (22) and even lower in the premature infant (2). In healthy adults it is found in plasma or serum in a concentration of 200 mg/l (= 2 μM, 22, 39). The half-life of the native (Glu-) plasminogen is 2.24 ± 0.29 days (6). Two types of Glu-plasminogen occur in human plasma, which differ in their carbohydrate composition as well as in their content of sialic acid. Genetic variants (see Mayr, 3.1.); of plasminogen have been reported (16) after isoelectric focusing of human plasma in polyacrylamide gels. Three patterns were found, two completely different and the third most likely a mixture of the other two. Characteristical functional properties of plasminogen are related to its molecular structure, e.g. its in vivo specificity for fibrin in contrast to the fairly unspecific in vitro activity of plasmin. Glu-plasminogen is easily converted by limited plasmic digestion to modified forms with NH₂-terminal lysine, valine or methionine (35, 36), which are commonly designated Lys-plasminogen” (26) displaying a plasma half-life time of 0,8 days (6). Lys-plasminogen forms are easily converted to plasmin which results in the formation of two-chain molecule (Lys-plasmin) from the single-chain monomer (zymogen).

Cytosolic Proteins Contribute to Surface Plasminogen Recruitment ofNeisseria meningitidis

“…Flow cytometric analyses have shown that all three receptors are present at the meningococcal surface, but at low levels. However, it is well known from other bacterial pathogens that plasminogen receptors can be present at the cell surface at very low levels, as plasminogen is highly abundant in many body fluids (serum concentrations, ϳ1.6 to 2 mol/liter, roughly corresponding to 100 to 200 mg/liter) (2,12,35,39). The presence of pneumococcal enolase, which has been shown to act as the major plasminogen receptor of S. pneumoniae, at the surfaces of these bacteria has been studied in detail (29).…”

The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor.

“…The fact that this binding is inhibitable in the presence of the lysine analogue tranexamic acid (Fig. 1J) indicates that plasminogen interacts with the surface of B. burgdorferi via its lysine-binding sites (27).…”

Plasminogen Is a Complement Inhibitor

“…The mobilities of the ␣Ј-and ␤-chains of the intact C3b protein are shown in lane 1. In the presence of ⑀ACA, aprotinin, or ␣ 2 -antiplasmin (␣2-AP), C3b cleavage was reduced (lanes [3][4][5]. Cleavage products generated by the complement serine protease Factor I in the presence of a cofactor (Factor H) were identified as ␣Ј68, ␣Ј43, and ␣Ј41 (lane 6).…”