Comparative immunohistochemical study of group II (synovial-type) and group IV (cytosolic) phospholipases A 2 in disc prolapse tissue

Abstract

IntroductionThe PLA2 isoforms include the secretory (also called synovial-type) group II extracellular 14 kD isoform (sPLA2) and the group IV cytosolic 85-110 kD isoforms (cPLA2) [6,21,22].It has been suggested that both types of PLA2 (sPLA2 and cPLA2) are implicated in inflammation. These enzymes catalyze the release of arachidonic acid, which is then converted, for instance, to prostaglandins by the cyclo-oxygenases (COX-1 and COX-2). Thus arachidonic acid mobilization seems to be dependent on both types of PLA2 [6,16,19,21,22].Abstract Phospholipase A 2 (PLA2) has been suggested to be present in herniated disc tissue and it could possibly be involved in sciatica/ discogenic back pain mechanisms. In the present study the occurrence of two different phospholipase A 2 enzymes, (1) low molecular weight (14 kDa) group II synovial-type (sPLA2) and (2) high molecular weight (85 kDa) group IV cytosolic (cPLA2), were compared. Fifty-three disc prolapses obtained at disc operations were analyzed by immunohistochemistry, using anti-human monoclonal antibodies to sPLA2 and cPLA2, respectively. Only cell-associated (disc cells, hyaline cartilage chondrocytes) sPLA2 and cPLA2 immunoreactivity could be observed. The results showed that sPLA2 was more common (25/53, 47%) than cPLA2 (13/53, 25%). sPLA2 and cPLA2 were simultaneously present in 13 of 53 samples (25%). However, both PLA2 enzymes were predominantly present in hyaline cartilage cells (sPLA2: 16/53, cPLA2: 5/53), being less commonly observed in disc cells (sPLA2: 6/53, cPLA2: 3/53). In addition, three samples for sPLA2 and two samples for cPLA2 exhibited immunoreactivity in cartilage and disc cells simultaneously. sPLA2 was observed in no other locations, but in 3 of 53 samples cPLA2 was observed more diffusely in areas of granulation tissue, possibly in macrophages. No gender-or age-related dependence for either type of PLA2 enzyme immunoreactivity could be observed. Neither did their occurrence relate to clinical data such as straight leg raising or neurological deficit. The results do not support a major role for either of the two disc-cell-associated PLA2s in disc pathophysiology. For both enzymes, the major pool appears to reside in cartilage tissue cells, presumably in dislodged end-plate fragments. Disc cells are apparently unlikely candidates for major PLA2 storage.

Nucleus pulposus-induced nerve root injury: effects of diclofenac and ketoprofen

“…However, in 1998 it was also reported that two different phospholipase A2 enzymes are present in herniated disc tissue from humans [14] and the difference in inhibitory effects of varying NSAIDs on these two enzyme types is, to our knowledge, still not known.…”

“…The reason for this difference is not known, but it might be related to the fact that ketoprofen and diclofenac belong to different NSAID subgroups and have a different selectivity for the two cyclo-oxygenases COX-1 and COX-2. ica induced by a herniated disc, in both recent and older literature [13,14,15,18,19,24,26,39,44,45,48]. Highdose administration of methylprednisolone, a potent antiinflammatory drug, has been shown in other experiments to reduce nucleus pulposus-induced nerve root injury dramatically [32].…”

Blood clots in vessels surrounding symptomatic nerve roots in disc herniation patients: a pilot study

“…Of note, platelets are a possible source of group II phospholipase A 2 (secretory PLA2: sPLA2), an enzyme that is involved in the amplification of both local and systemic inflammation [1, 7, 8], and has been suggested to be involved in disc pathophysiology and possibly also sciatica [27,29]. Controlled studies have suggested that PLA2 levels are not pathologically high in disc herniation tissue or degenerated discs in comparison with control disc tissues [10,11], and thus alternative sources of PLA2 enzyme, such as release from platelets, may be clinically relevant. PLA2 enzyme has been shown to have deleterious effects on nerve root function and structure in an animal model [5].…”

“…Platelets are known to contain both a low molecular weight (14 kDa, sPLA2) and a higher molecular weight (85 kDa, cytosolic: cPLA2) PLA2 enzyme, which are located in the α-granules and the cytosol of platelets, respectively. It has [11]. Platelet activation follows adhesion, which is triggered by damage of the blood vessel wall [22].…”